Impact of Intracranial Aneurysm Morphology and Rupture Status on the Particle Residence Time.

BACKGROUND AND PURPOSE: Aneurysm hemodynamics play an important role in aneurysm growth and subsequent rupture. Within the available hemodynamic characteristics, particle residence time (PRT) is relatively unexplored. However, some studies have shown that PRT is related to thrombus formation and inflammation. The goal of this study is to evaluate the association between PRT and aneurysm rupture and morphology. METHODS: We determined the PRT for 113 aneurysms (61 unruptured, 53 ruptured) based on computational fluid dynamic models. Virtual particles were injected into the parent vessel and followed during multiple cardiac cycles. PRT was defined as the time needed for 99% of the particles that entered an aneurysm to leave the aneurysm. Subsequently, we evaluated the association between PRT, rupture, and morphology (aneurysm type, presence of blebs, or multiple lobulations). RESULTS: PRT showed no significant difference between unruptured (1.1 seconds interquartile range [IQR .39-2.0 seconds]) and ruptured aneurysms (1.2 seconds [IQR .47-2.3 seconds]). PRT was influenced by aneurysm morphology. Longer PRTs were seen in bifurcation aneurysms (1.3 seconds [IQR .54-2.4 seconds], P = .01) and aneurysms with blebs or multiple lobulations (1.92 seconds [IQR .94-2.8 seconds], P < .001). Four of five partially thrombosed aneurysms had a long residence time (>1.9 seconds). CONCLUSIONS: Our study shows an influence of aneurysm morphology on PRT. Nevertheless, it suggests that PRT cannot be used to differentiate unruptured and ruptured aneurysms.

Aneurysmal Parent Artery-Specific Inflow Conditions for Complete and Incomplete Circle of Willis Configurations.

BACKGROUND AND PURPOSE: Hemodynamics are thought to play a role in intracranial aneurysm growth and rupture. Computational fluid dynamics is frequently performed to assess intra-aneurysmal hemodynamics, using generalized flow waveforms of healthy volunteers as inflow boundary conditions. The purpose of this study was to assess differences in inflow conditions for different aneurysmal parent artery locations and variations of circle of Willis configurations. MATERIALS AND METHODS: In a series of 96 patients with 103 aneurysms, velocity measurements were acquired using 2D phase-contrast MR imaging perpendicular to the aneurysmal parent arteries in the circle of Willis. Circle of Willis configurations were inspected for variations using multiple overlapping thin-slab-acquisition MRAs. Flow rates, velocity magnitudes, and pulsatility indices were calculated for each parent artery location in subgroups of complete and incomplete circle of Willis configurations. RESULTS: Flow rates, velocity magnitudes, and pulsatility indices were significantly different among aneurysmal parent arteries. Incomplete circle of Willis configurations were observed in 24% of the cases. Significantly lower basilar artery flow rates were observed in configurations with hypoplastic P1 segments. Significantly higher A1 flow rates were observed in configurations with a hypoplastic contralateral A1 segment. CONCLUSIONS: Inflow conditions vary substantially between aneurysmal parent arteries and circle of Willis configurations. We have created a collection of parent artery-specific inflow conditions tailored to the patient-specific circle of Willis configuration that can be used in future computational fluid dynamics studies analyzing intra-aneurysmal hemodynamics.

Avaliação nutricional do resíduo desidratado de cervejaria para coelhos em crescimento / Nutritional evaluation of dried brewer for growing rabbits

Foi conduzido um ensaio de digestibilidade para determinar o valor nutritivo do resíduo desidratado de cervejaria (RDC) e outro para verificar o desempenho de coelhos em crescimento alimentados com rações contendo diferentes níveis de RDC e a viabilidade econômica da utilização do RDC. No ensaio de digestibilidade, foram utilizados 20 coelhos, de ambos os sexos, da raça Nova Zelândia Branco, com idade média de 45 dias, distribuídos em delineamento experimental inteiramente ao acaso, com dois tratamentos, sendo uma dieta referência e outra dieta teste, na qual o RDC substituiu a ração referência em nível de 30%. Os coeficientes de digestibilidade aparente (CDA) da matéria seca (MS), da energia bruta (EB), da proteína bruta (PB) do RDC foram de 49,97%, 49,34%, e 71,06%, respectivamente, com valores de energia digestível (ED) e proteína digestível (PD) do RDC, com base na matéria seca, de 2330,60kcal/kg e 15,75%. No experimento de desempenho, foram avaliadas rações com níveis de inclusão de RDC de 0%, 5%, 10%, 15%, 20% e 25%. Foram utilizados 120 coelhos da raça Nova Zelândia Branco, 60 machos e 60 fêmeas, com 32 dias de idade, em delineamento experimental inteiramente ao acaso, com seis tratamentos e 10 repetições, sendo a unidade experimental constituída por dois animais. Não foram observadas diferenças no desempenho dos coelhos alimentados com ração contendo níveis crescentes de RDC, exceto para a conversão alimentar aos 70 dias, que apresentou efeito quadrático no período dos 32 aos 70 dias de idade, com a pior conversão alimentar ao nível de 16,95% de RDC. No entanto, houve redução linear nos custos com alimentação, por quilo de ganho de peso dos animais. Conclui-se que o resíduo desidratado de cervejaria apresenta CDA equivalente aos ingredientes convencionais, podendo ser incluído até o nível máximo estudado de 25% nas rações de coelhos em crescimento, sem prejudicar o desempenho.(AU)

Two experiments were conducted, being a digestibility assay in order to determine the nutritive value of dehydrated diets containing different levels of DBR, and the economic viability of the use of DRC brewer residue (DBR) and other assays to verify the performance of growing rabbits fed. In the digestibility experiment, twenty White New Zealand rabbits were used, with an average age of 45 days, of both genders, distributed in a completely randomized design with four treatments, one reference diet and other test diets, in which the DBR replaced the basal diet at 30% level. The apparent digestibility coefficients (ADC) of dry matter (DM), gross energy (GE), crude protein (CP) of DBR were, respectively, 49.97%, 49.34% and 71.06%. The values of digestible energy (DE) and digestible protein (DP) of the DBR, based on dry matter, were 2330.60kcal/kg and 15.75%. In the performance experiment, diets with levels of DBR inclusion of 0%, 5%, 10%, 15%, 20% and 25% were evaluated. One hundred and twenty 32 days old New Zealand White rabbits were used, being 60 males and 60 females, distributed in a completely randomized design with six treatments and ten replicates, and the experimental unit consisted of two animals. No differences (P>0.05) were observed in the performance of rabbits fed diets containing increasing levels of dehydrated brewer residue, except for feed conversion at 70 days which presented a quadratic effect, with the worst results at the level of 16.95% of the DBR inclusion in the diet. It is concluded that the dehydrated brewer residue has good nutritional value and can be included up to the maximum level studied of 25% in the diets of growing rabbits, with no damage to its performance.(AU)

Digestibilidade de nutrientes em rações de frangos de corte suplementadas com promotores de crescimento / Nutrient digestibility in diets for broilers supplemented with growth promoters

Um experimento foi realizado para avaliar o efeito da utilização de diferentes promotores de crescimento sobre o metabolismo de frangos de corte em crescimento. Foram avaliadas duas dietas, uma atendendo às exigências nutricionais de frangos de corte (normal) e uma dieta reduzida, com 5% a menos da exigência nutricional (reduzida), suplementadas ou não com antibióticos e prebióticos. Foram utilizados 180 pintos de corte criados em galpão convencional, com cama de maravalha, até os 21 dias de idade. Em seguida, foram divididos em 36 gaiolas, distribuídos em delineamento experimental inteiramente ao acaso, utilizando método tradicional de coleta de excretas. Houve interação (P<0,05) entre dieta e promotores de crescimento para os coeficientes de digestibilidade ileal da matéria seca (CDIMS), da proteína bruta (CDIPB) e do extrato etéreo (CDIEE). A dieta reduzida contendo antibiótico apresentou menor CDIMS. A dieta normal contendo antibiótico apresentou maior CDIPB (P<0,05), enquanto a dieta reduzida contendo prebiótico apresentou melhor CDIPB e CDIEE (P<0,05). Os valores dos coeficientes de digestibilidade total da matéria seca (CDTMS), da proteína bruta (CDTPB) e do extrato etéreo (CDTEE) apresentaram interação (P<0,05) entre dietas e promotores de crescimento, em que a dieta reduzida contendo antibiótico apresentou menor CDTMS e CDTEE. A dieta normal apresentou maiores valores de energia metabolizável aparente (EMA) e EMA corrigida para balanço de nitrogênio (EMAn) (P<0,05). Concluiu-se que, ao se reduzir a exigência nutricional da ração, a digestibilidade dos nutrientes foi reduzida, no entanto os óleos essenciais promoveram aumento nos coeficientes de digestibilidade ileal da matéria seca, da proteína bruta e do extrato etéreo.

An experiment was conducted to evaluate the effect of using different growth promoters on the metabolism of growing broilers. We evaluated two diets, one meeting the nutritional requirements of broilers (normal) and another reduced diet with 5% less than the nutritional requirement (reduced), supplemented or not with antibiotics and prebiotics. A total of 180 broiler chicks reared in shed masonry and wood shaving bedding until 21 days of age. The animals were divided into 36 cages and distributed in a completely randomized design, using a traditional method of excreta collection. There was an interaction (P<0.05) between diet and growth promoters for ileal digestibility coefficient of dry matter (IDCDM), crude protein (IDCCP) and ether extract (IDCEE). The reduced diet containing antibiotics had lower IDCDM. The normal diet containing antibiotic had higher IDCCP (P<0.05), whereas the reduced diet containing prebiotic showed better IDCCP and IDCEE (P<0.05). The values of total digestibility coefficient of dry matter (TDCDM), crude protein (TDCCP) and ether extract (TDCEE) showed interaction (P<0.05) between diets and growth promoters, where the reduced diet containing antibiotics had lower TDCDM and TDCEE. A normal diet had higher apparent metabolizable energy (AME) and AME corrected for nitrogen balance (AMEn) (P<0.05). It was concluded that when the nutritional requirement of diet was reduced, the nutrients digestibility was also reduced, however essential oils caused an increase in ileal digestibility of dry matter, crude protein and ether extract.

Additional Value of Intra-Aneurysmal Hemodynamics in Discriminating Ruptured versus Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Hemodynamics are thought to play an important role in the rupture of intracranial aneurysms. We tested whether hemodynamics, determined from computational fluid dynamics models, have additional value in discriminating ruptured and unruptured aneurysms. Such discriminative power could provide better prediction models for rupture. MATERIALS AND METHODS: A cross-sectional study was performed on patients eligible for endovascular treatment, including 55 ruptured and 62 unruptured aneurysms. Association with rupture status was tested for location, aneurysm type, and 4 geometric and 10 hemodynamic parameters. Patient-specific spatiotemporal velocities measured with phase-contrast MR imaging were used as inflow conditions for computational fluid dynamics. To assess the additional value of hemodynamic parameters, we performed 1 univariate and 2 multivariate analyses: 1 traditional model including only location and geometry and 1 advanced model that included patient-specific hemodynamic parameters. RESULTS: In the univariate analysis, high-risk locations (anterior cerebral arteries, posterior communicating artery, and posterior circulation), daughter sacs, unstable inflow jets, impingements at the aneurysm body, and unstable complex flow patterns were significantly present more often in ruptured aneurysms. In both multivariate analyses, only the high-risk location (OR, 3.92; 95% CI, 1.77-8.68) and the presence of daughter sacs (OR, 2.79; 95% CI, 1.25-6.25) remained as significant independent determinants. CONCLUSIONS: In this study population of patients eligible for endovascular treatment, we found no independent additional value of aneurysmal hemodynamics in discriminating rupture status, despite high univariate associations. Only traditional parameters (high-risk location and the presence of daughter sacs) were independently associated with ruptured aneurysms.

Hemodynamic Differences in Intracranial Aneurysms before and after Rupture.

BACKGROUND AND PURPOSE: Rupture risk of intracranial aneurysms may depend on hemodynamic characteristics. This has been assessed by comparing hemodynamic data of ruptured and unruptured aneurysms. However, aneurysm geometry may change before, during, or just after rupture; this difference causes potential changes in hemodynamics. We assessed changes in hemodynamics in a series of intracranial aneurysms, by using 3D imaging before and after rupture. MATERIALS AND METHODS: For 9 aneurysms in 9 patients, we used MRA, CTA, and 3D rotational angiography before and after rupture to generate geometric models of the aneurysm and perianeurysmal vasculature. Intra-aneurysmal hemodynamics were simulated by using computational fluid dynamics. Two neuroradiologists qualitatively assessed flow complexity, flow stability, inflow concentration, and flow impingement in consensus, by using flow-velocity streamlines and wall shear stress distributions. RESULTS: Hemodynamics changed in 6 of the 9 aneurysms. The median time between imaging before and after rupture was 678 days (range, 14-1461 days) in these 6 cases, compared with 151 days (range, 34-183 days) in the 3 cases with unaltered hemodynamics. Changes were observed for flow complexity (n = 3), flow stability (n = 3), inflow concentration (n = 2), and region of flow impingement (n = 3). These changes were in all instances associated with aneurysm displacement due to rupture-related hematomas, growth, or newly formed lobulations. CONCLUSIONS: Hemodynamic characteristics of intracranial aneurysms can be altered by geometric changes before, during, or just after rupture. Associations of hemodynamic characteristics with aneurysm rupture obtained from case-control studies comparing ruptured with unruptured aneurysms should therefore be interpreted with caution.

Generalized versus patient-specific inflow boundary conditions in computational fluid dynamics simulations of cerebral aneurysmal hemodynamics.

BACKGROUND AND PURPOSE: Attempts have been made to associate intracranial aneurysmal hemodynamics with aneurysm growth and rupture status. Hemodynamics in aneurysms is traditionally determined with computational fluid dynamics by using generalized inflow boundary conditions in a parent artery. Recently, patient-specific inflow boundary conditions are being implemented more frequently. Our purpose was to compare intracranial aneurysm hemodynamics based on generalized versus patient-specific inflow boundary conditions. MATERIALS AND METHODS: For 36 patients, geometric models of aneurysms were determined by using 3D rotational angiography. 2D phase-contrast MR imaging velocity measurements of the parent artery were performed. Computational fluid dynamics simulations were performed twice: once by using patient-specific phase-contrast MR imaging velocity profiles and once by using generalized Womersley profiles as inflow boundary conditions. Resulting mean and maximum wall shear stress and oscillatory shear index values were analyzed, and hemodynamic characteristics were qualitatively compared. RESULTS: Quantitative analysis showed statistically significant differences for mean and maximum wall shear stress values between both inflow boundary conditions (P < .001). Qualitative assessment of hemodynamic characteristics showed differences in 21 cases: high wall shear stress location (n = 8), deflection location (n = 3), lobulation wall shear stress (n = 12), and/or vortex and inflow jet stability (n = 9). The latter showed more instability for the generalized inflow boundary conditions in 7 of 9 patients. CONCLUSIONS: Using generalized and patient-specific inflow boundary conditions for computational fluid dynamics results in different wall shear stress magnitudes and hemodynamic characteristics. Generalized inflow boundary conditions result in more vortices and inflow jet instabilities. This study emphasizes the necessity of patient-specific inflow boundary conditions for calculation of hemodynamics in cerebral aneurysms by using computational fluid dynamics techniques.

Rupture-associated changes of cerebral aneurysm geometry: high-resolution 3D imaging before and after rupture.

BACKGROUND AND PURPOSE: Comparisons of geometric data of ruptured and unruptured aneurysms may yield risk factors for rupture. Data on changes of geometric measures associated with rupture are, however, sparse, because patients with ruptured aneurysms rarely have undergone previous imaging of the intracranial vasculature. We had the opportunity to assess 3D geometric differences of aneurysms before and after rupture. The purpose of this study was to evaluate possible differences between prerupture and postrupture imaging of a ruptured intracranial aneurysm. MATERIALS AND METHODS: Using high-quality 3D image data, we generated 3D geometric models before and after rupture and compared these for changes in aneurysm volume and displacement. A neuroradiologist qualitatively assessed aneurysm shape change, the presence of perianeurysmal hematoma, and subsequent mass effect exerted on aneurysm and parent vessels. RESULTS: Aneurysm volume was larger in the postrupture imaging in 7 of 9 aneurysms, with a median increase of 38% and an average increase of 137%. Three aneurysms had new lobulations on postrupture imaging; 2 other aneurysms were displaced up to 5 mm and had changed in geometry due to perianeurysmal hematoma. CONCLUSIONS: Geometric comparisons of aneurysms before and after rupture show a large volume increase, origination of lobulations, and displacement due to perianeurysmal hematoma. Geometric and hemodynamic comparison of series of unruptured and ruptured aneurysms in the search for rupture-risk-related factors should be interpreted with caution.

3D cine phase-contrast MRI at 3T in intracranial aneurysms compared with patient-specific computational fluid dynamics.

BACKGROUND AND PURPOSE: CFD has been proved valuable for simulating blood flow in intracranial aneurysms, which may add to better rupture risk assessment. However, CFD has drawbacks such as the sensitivity to assumptions needed for the model, which may hinder its clinical implementation. 3D PC-MR imaging is a technique that enables measurements of blood flow. The purpose of this study was to compare flow patterns on the basis of 3D PC-MR imaging with CFD estimates. MATERIALS AND METHODS: 3D PC-MR imaging was performed in 8 intracranial aneurysms. Two sets of patient-specific inflow boundaries for CFD were obtained from a separate 2D PC-MR imaging sequence (2D CFD) and from the 3D PC-MR imaging (3D CFD) data. 3D PC-MR imaging and CFD were compared by calculation of the differences between velocity vector magnitudes and angles. Differences in flow patterns expressed as the presence and strengths of vortices were determined by calculation of singular flow energy. RESULTS: In systole, flow features such as vortex patterns were similar. In diastole, 3D PC-MR imaging measurements appeared inconsistent due to low velocity-to-noise ratios. The relative difference in velocity magnitude was 67.6 ± 51.4% and 27.1 ± 24.9% in systole and 33.7 ± 21.5% and 17.7 ± 10.2% in diastole for 2D CFD and 3D CFD, respectively. For singular energy, this was reduced to 15.5 ± 13.9% at systole and 19.4 ± 17.6% at diastole (2D CFD). CONCLUSIONS: In systole, good agreement between 3D PC-MR imaging and CFD on flow-pattern visualization and singular-energy calculation was found. In diastole, flow patterns of 3D PC-MR imaging differed from those obtained from CFD due to low velocity-to-noise ratios.

Intracranial aneurysm neck size overestimation with 3D rotational angiography: the impact on intra-aneurysmal hemodynamics simulated with computational fluid dynamics.

BACKGROUND AND PURPOSE: 3DRA is considered the reference standard for the assessment of intracranial aneurysm morphology. However, it has been shown that 3DRA may overestimate neck size compared with 2D DSA. The purpose of this study was to determine the impact of neck size overestimation with 3DRA on intra-aneurysmal hemodynamics. MATERIALS AND METHODS: In a series of 20 patients, 20 intracranial aneurysms were analyzed for aneurysm neck size overestimation with 3DRA compared with 2D DSA. 3DRA-derived vascular models were modified to agree with 2D DSA. Geometric and hemodynamic variables of the original and modified vascular models were compared. RESULTS: In 8 of the 20 evaluated cases, 3DRA-derived aneurysm models showed neck size overestimation compared with 2D DSA images. The average neck diameter reduction after modification was 19%, which was, on average, 0.85 mm (±0.32 mm). Modification of the neck resulted in differences in location of inflow jet (2/8), impingement zone (3/8), and low WSS area (4/8). In 1 case, the maximal WSS increased by 98% after modification. The change of impingement zone location resulted in a different classification of the impingement zone region in 2 cases. CONCLUSIONS: Neck size overestimation on 3DRA can have non-negligible consequences for hemodynamic features determined with CFD.

A flow-diverting stent is not a pressure-diverting stent.

The approach for treatment of large and fusiform intracranial aneurysms has evolved from stent-assisted coiling to treatment with flow-diverting stents. The treatment results for these stents are promising; however, early postprocedural aneurysm rupture has been described. The exact cause of rupture is unknown but might be related to intra-aneurysmal flow and pressure changes. We measured intra-aneurysmal pressure before, during, and after placement of a flow-diverting stent by using a dual-sensor guidewire. The pressure inside the aneurysm momentarily decreased during placement but was restored to baseline values within minutes. The flow-diverting stent does not seem to protect the aneurysm from the stress induced by pressure or pressure changes within the lumen.

Comparison of phase-contrast MR imaging and endovascular sonography for intracranial blood flow velocity measurements.

BACKGROUND AND PURPOSE: Local hemodynamic information may help to stratify rupture risk of cerebral aneurysms. Patient-specific modeling of cerebral hemodynamics requires accurate data on BFV in perianeurysmal arteries as boundary conditions for CFD. The aim was to compare the BFV measured with PC-MR imaging with that obtained by using intra-arterial Doppler sonography and to determine interpatient variation in intracranial BFV. MATERIALS AND METHODS: In 10 patients with unruptured intracranial aneurysms, BFV was measured in the cavernous ICA with PC-MR imaging in conscious patients before treatment, and measured by using an intra-arterial Doppler sonography wire when the patient was anesthetized with either propofol (6 patients) or sevoflurane (4 patients). RESULTS: Both techniques identified a pulsatile blood flow pattern in cerebral arteries. PSV differed >50 cm/s between patients. A mean velocity of 41.3 cm/s (95% CI, 39.3-43.3) was measured with PC-MR imaging. With intra-arterial Doppler sonography, a mean velocity of 29.3 cm/s (95% CI, 25.8-32.8) was measured with the patient under propofol-based intravenous anesthesia. In patients under sevoflurane-based inhaled anesthesia, a mean velocity of 44.9 cm/s (95% CI, 40.6-49.3) was measured. CONCLUSIONS: We showed large differences in BFV between patients, emphasizing the importance of using patient-specific hemodynamic boundary conditions in CFD. PC-MR imaging measurements of BFV in conscious patients were comparable with those obtained with the intra-arterial Doppler sonography when the patient was anesthetized with a sevoflurane-based inhaled anesthetic.

Complex flow patterns in a real-size intracranial aneurysm phantom: phase contrast MRI compared with particle image velocimetry and computational fluid dynamics.

The aim of this study was to validate the flow patterns measured by high-resolution, time-resolved, three-dimensional phase contrast MRI in a real-size intracranial aneurysm phantom. Retrospectively gated three-dimensional phase contrast MRI was performed in an intracranial aneurysm phantom at a resolution of 0.2 × 0.2 × 0.3 mm(3) in a solenoid rat coil. Both steady and pulsatile flows were applied. The phase contrast MRI measurements were compared with particle image velocimetry measurements and computational fluid dynamics simulations. A quantitative comparison was performed by calculating the differences between the magnitude of the velocity vectors and angles between the velocity vectors in corresponding voxels. Qualitative analysis of the results was executed by visual inspection and comparison of the flow patterns. The root-mean-square errors of the velocity magnitude in the comparison between phase contrast MRI and computational fluid dynamics were 5% and 4% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 16° and 14° for the steady and pulsatile measurements, respectively. In the phase contrast MRI and particle image velocimetry comparison, the root-mean-square errors were 12% and 10% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 19° and 15° for the steady and pulsatile measurements, respectively. Good agreement was found in the qualitative comparison of flow patterns between the phase contrast MRI measurements and both particle image velocimetry measurements and computational fluid dynamics simulations. High-resolution, time-resolved, three-dimensional phase contrast MRI can accurately measure complex flow patterns in an intracranial aneurysm phantom.

Intracranial blood-flow velocity and pressure measurements using an intra-arterial dual-sensor guidewire.

Hemodynamics is thought to play a role in the growth and rupture of intracranial aneurysms. In 4 patients, we obtained local pressure and BFV by using a dual-sensor pressure and Doppler velocity wire within and in vessels surrounding unruptured aneurysms. Local BFVs can serve as boundary conditions for computational fluid dynamics, whereas pressure recordings provide direct information on the mechanical load imposed on the aneurysm. Both measurements may thus add to patient-specific rupture-risk assessment.

Neighbourhood socioeconomic disadvantage and behavioural problems from late childhood into early adolescence.

STUDY OBJECTIVE: This study investigates whether neighbourhood socioeconomic disadvantage may contribute to child behavioural and emotional problems, beyond the effects of parental socioeconomic status. It also examines the influence of neighbourhood disadvantage on changes in the frequency of behavioural problems from late childhood into early adolescence. DESIGN AND SETTING: The study was conducted in a large community sample in Rotterdam, the Netherlands. An index of neighbourhood socioeconomic disadvantage was calculated for each of the city's 74 neighbourhoods. Multilevel regression analysis estimated effects of neighbourhood disadvantage and individual variables (parental socioeconomic status, child's gender, and age) on behavioural problems reported by children (Youth Self-Report) and parents (Child Behavior Checklist) and on changes in these scores over a two year follow up. PARTICIPANTS: A cohort of all children born in 1978 and living in Rotterdam. Of those eligible, 73% (n=2587) participated in the first measurement (T1), at 10-12 years; 71% of the T1 respondents participated again two years later (T2), at 12-14 years. MAIN RESULTS: Neighbourhood disadvantage was associated with higher Total, Internalising, and Externalising Problems, as assessed with both the Child Behavior Checklist and the Youth Self-Report, even after controlling for parental socioeconomic status. Neighbourhood disadvantage also seemed to contribute to increases in Total Problems over the follow up. CONCLUSIONS: Living in a disadvantaged neighbourhood is associated with greater behavioural problems and may lead to an exacerbation of problems as children move from childhood into adolescence. Public health interventions to improve child mental health must take the neighbourhood environment into account.

Predicting outcome of anterior temporal lobectomy using simulated neural networks.

PURPOSE: Anterior temporal lobectomy (ATL) is an important option for treatment of medically refractory seizures. Patient selection is not always clear-cut, and there is inherent morbidity and mortality associated with the invasive and expensive surgical protocols. To determine whether patient selection might be facilitated by application of artificial intelligence, we developed a model that predicted seizure outcome after ATL, using a simulated neural network (SNN). METHODS: Predictions of the model were compared with predictions derived from conventional discriminant function analysis. Neural networks and discriminant functions were devised that would predict the occurrence of both Class 1 outcomes (totally seizure-free), and Class 1 or Class 2 outcomes (nearly or totally seizure-free), using data from 87 patients from three surgical centers. The SNNs and discriminant functions were developed using data from a randomly selected subsample of 65 patients, and both models were cross-validated, using the remaining 22 patients. RESULTS: The discriminant functions showed overall predictive accuracy of 78.5% and 72.7%, while the neural networks demonstrated overall accuracy of 81.8% and 95.4%. CONCLUSIONS: Simulated neural networks show promise as adjuncts to decision-making in the selection of epilepsy surgery patients.

Identification of N(G)-methylarginine residues in human heterogeneous RNP protein A1: Phe/Gly-Gly-Gly-Arg-Gly-Gly-Gly/Phe is a preferred recognition motif.

Three sites of N(G),N(G)-arginine methylation have been located at residues 205, 217, and 224 in the glycine-rich, COOH-terminal one-third of the HeLa A1 heterogeneous ribonucleoprotein. Together with the previously determined dimethylated arginine at position 193 [Williams et al., (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5666-5670], it is evident that all four sites fall within a span of sequence between residues 190 and 233 that contains multiple Arg-Gly-(Gly) sequences interspersed with phenylalanine residues. These RGG boxes have been postulated to represent an RNA binding motif [Kiledjian and Dreyfuss (1992) EMBO J. 11, 2655-2664]. Dimethylation of HeLa A1 appears to be quantitative at each of the four positions. Arginines 205 and 224 have been methylated in vitro by a nuclear protein arginine methyltransferase using recombinant (unmethylated) A1 as substrate. This suggests A1 may be an in vivo substrate for this enzyme. Examination of sequences surrounding the sites of methylation in A1 along with a compilation from the literature of sites that have been identified in other nuclear RNA binding proteins suggests a methylase-preferred recognition sequence of Phe/Gly-Gly-Gly-Arg-Gly-Gly-Gly/Phe, with the COOH-terminal flanking glycine being obligatory. Taken together with data in the literature, identification of the sites of A1 arginine methylation strongly suggests a role for this modification in modulating the interaction of A1 with nucleic acids.

Psychological and Neurobehavioral Disorders in MSA Health-Oriented, Rehabilitative Perspective.

In this article, the authors discuss the classification, recognition, and rehabilitation team management of psychological and neurobehavioral disorders in multiple sclerosis (MS), emphasizing throughout their view that from the psychological standpoint, MS is preeminently a disorder of the patient's self or identity. Disorders of the process of normal adjustment, disorders of organization and control (including disorders of affect and of cognition), and disorders of personality functioning are considered in turn. Finally, the authors discuss a model for the role of comprehensive, inpatient rehabilitation team treatment in addressing MS-related neurobehavioral disorders.

Neuroscience, modularity and personality theory: conceptual foundations of a model of complex human functioning.

The purpose of this paper is to lay the groundwork for the development of a scientific theory of complex human functioning. We first discuss the assumptions on which our thinking is based, then advance the argument that behavior, and human activity in general, may be more fully understood in light of current data on the structural organization of the central nervous system. The brain is organized as a modular, distributed, self-organizing system, which is in constant transaction with the environment. Because of its plasticity, structural and functional change occurs in the brain as a result of experience throughout life. It is our thesis that complex human behavior is organized in a similar manner - that is, human personality and behavior manifest themselves as modular systems. The insights provided by an understanding of the relationship of brain and behavior may enhance the capacity to explain both normal and pathological personality functioning.